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Placement of deep brain stimulators into the subthalamic nucleus or Globus pallidus internus: technical approach.

Deep brain stimulation (DBS) represents a major advance in the treatment of Parkinson's disease (PD). As more neurosurgeons enter this field, technical descriptions of implantation techniques are needed. Here we present our technical approach to subthalamic nucleus (STN) and globus pallidus internus (GPi) DBS implantation, based on 180 STN implants and 75 GPi implants. The essential steps in DBS implantation are magnetic resonance imaging (MRI)-guided stereotactic localization, confirmation of the motor territory of the target nucleus with microelectrode mapping, and intra-operative test stimulation to determine voltage thresholds for stimulation-induced adverse effects. Lead locations are documented by postoperative MRI in all cases.

Dystonia↗

Long-term follow-up of thalamic deep brain stimulation for essential and parkinsonian tremor.

Thirteen consecutive patients with thalamic deep brain stimulation (DBS) were examined serially for 3 to 5 years. Initially, all demonstrated at least 50% improvement in contralateral tremor. At last follow-up, three of eight patients with Parkinson disease no longer used DBS because tremor had markedly improved, and for two, motor fluctuations and levodopa-induced dyskinesias became the major disability, with tremor less troublesome. Two of five patients with essential tremor had contralateral tremor improvement after ongoing stimulation for 2 years; two developed marked tolerance to DBS.

Adult↗

Deep brain stimulation for essential tremor.

We examined the effects and safety of deep brain stimulation (DBS) as a treatment for essential tremor (ET). Ten ET patients with disabling medication-refractory tremor underwent stereotactic implantation of a DBS lead in the left Vim thalamic nucleus and completed a 6-month follow-up. The Clinical Tremor Rating Scale and disability assessments were performed at baseline, 1-, 3-, and 6-month follow-up. There were significant improvements in dressing, drinking, eating, bathing, and handwriting as reported by the subjects. Tremor severity, writing, pouring, and spiral and line drawing were significantly improved as rated by the examiner. Improvements persisted through the 6-month follow-up period. Although global disability significantly lessened in the group as a whole, one subject with hand-finger tremor accentuated by writing had no change in disability status. In this 6-month open-label study, DBS was effective and safe in reducing tremor and functional disability in ET.

Aged↗

Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation.

OBJECTIVE: To compare the effects of unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) with bilateral STN DBS in advanced PD. METHODS: Our initial 10 consecutive patients with medication-refractory motor fluctuations and levodopa-induced dyskinesias undergoing chronic bilateral STN DBS underwent a standardized evaluation of unilateral and bilateral STN DBS in the medication-off state 6 to 18 months after electrode implantation. RESULTS: Bilateral STN DBS improved the mean total Unified Parkinson's Disease Rating Scale motor score by 54%, whereas unilateral stimulation improved motor scores only 23%. Unilateral STN DBS improved postural stability and gait 14%, other axial motor features 19%, and overall parkinsonism in limbs contralateral to stimulation by 46%, including an 86% improvement in contralateral tremor. However, bilateral STN DBS resulted in greater improvement in each of these domains, including limb function, i.e., the reduction in scores from the limbs on one side was greater with bilateral than with unilateral stimulation of the contralateral STN. CONCLUSIONS: Bilateral STN DBS improves parkinsonism considerably more than unilateral STN DBS; bilateral simultaneous electrode implantation may be the most appropriate surgical option for patients with significant bilateral disability. Unilateral STN DBS results in moderate improvement in all aspects of off-period parkinsonism and improves tremor as much as is typically reported with DBS of the ventral intermedius nucleus of the thalamus (Vim). For this reason, STN DBS may be a more appropriate choice than Vim DBS or thalamotomy for parkinsonian tremor. Some patients with highly asymmetric tremor-dominant PD might be appropriately treated with unilateral instead of bilateral STN DBS.

Aged↗

Deep brain stimulation for movement disorders: morbidity and mortality in 109 patients.

OBJECT: Deep brain stimulation (DBS) has been advocated as a more highly effective and less morbidity-producing alternative to ablative stereotactic surgery in the treatment of medically intractable movement disorders. Nevertheless, the exact incidence of morbidity and mortality associated with the procedure is not well known. In this study the authors reviewed the surgical morbidity and mortality rates in a large series of DBS operations. METHODS: The authors retrospectively analyzed surgical complications in their consecutive series of 179 DBS implantations in 109 patients performed by a single surgical team at one center between July 1998 and April 2002. The mean follow-up period was 20 months. There were 16 serious adverse events related to surgery in 14 patients (12.8%). There were two perioperative deaths (1.8%), one caused by pulmonary embolism and the second due to aspiration pneumonia. The other adverse events were two pulmonary embolisms, two subcortical hemorrhages, two chronic subdural hematomas, one venous infarction, one seizure, four infections, one cerebrospinal fluid leak, and one skin erosion. The incidence of permanent sequelae was 4.6% (five of 109 patients). The incidence of device-related complications, such as infection or skin erosion, was also 4.6% (five of 109 patients). CONCLUSIONS: There is a significant incidence of adverse events associated with the DBS procedure. Nevertheless, DBS is clinically effective in well-selected patients and should be seriously considered as a treatment option for patients with medically refractory movement disorders.

Adult↗

A review of the treatment for refractory obsessive-compulsive disorder: from medicine to deep brain stimulation.

This article provides an overview of the etiology, epidemiology, and first-line treatment options for obsessive-compulsive disorder (OCD). The subject of treatment-resistant and treatment-refractory OCD is then discussed, including a definition of these often-debated terms, and the latest treatment options delineated. This includes a review of the latest research concerning the pharmacological agents that have been studied as monotherapy or augmenting agents for the treatment of OCD, the use of experimental medications and procedures, treatment with reversible, minimally invasive procedures, such as vagal nerve stimulation and transcranial magnetic stimulation, invasive but the potentially reversible deep brain stimulation, and irreversible lesioning with ablative psychosurgery. A discussion of the role of psychotherapy in the treatment of OCD is also included.

Antipsychotic Agents↗

Hypothalamic deep brain stimulation in positron emission tomography.

Recently, functional imaging data have underscored the crucial role the hypothalamus plays in cluster headache, one of the most severe forms of primary headache. This prompted the application of hypothalamic deep brain stimulation. Yet, it is not apparent how stimulation of an area that is thought to act as a pace-maker for acute headache attacks is able to prevent these attacks from occurring. We addressed this issue by examining 10 operated chronic cluster headache patients, using H2(15O)-positron emission tomography and alternately switching the hypothalamic stimulator on and off. The stimulation induced activation in the ipsilateral hypothalamic gray (the site of the stimulator tip), the ipsilateral thalamus, somatosensory cortex and praecuneus, the anterior cingulate cortex, and the ipsilateral trigeminal nucleus and ganglion. We additionally observed deactivation in the middle temporal gyrus, posterior cingulate cortex, and contralateral anterior insula. Both activation and deactivation are situated in cerebral structures belonging to neuronal circuits usually activated in pain transmission and notably in acute cluster headache attacks. Our data argue against an unspecific antinociceptive effect or pure inhibition of hypothalamic activity. Instead, the data suggest a hitherto unrecognized functional modulation of the pain processing network as the mode of action of hypothalamic deep brain stimulation in cluster headache.

Adult↗

Deep brain stimulation of globus pallidus internus for dystonia.

Neuromodulation is the functional modification of neural structures through the use of electrical stimulation. Its most clinically applicable use is deep brain stimulation (DBS) of basal ganglia structures in Parkinson's disease (PD) and essential tremor (ET). More recently, it has been used as a means of treating dystonic movement disorders. The main target of DBS for dystonia is the posteroventral globus pallidus internus (GPi), although the thalamus has been used as an alternate target in a minority of cases. In comparison to the effects seen in PD, the improvement in dystonic postures appear to differ in several ways--delay of clinical benefit, higher voltage requirements, and varied stimulator settings. In this review, the authors discuss the clinical characteristics, pathophysiology, microelectrode recording (MER) signatures, optimal surgical targets, programming parameters and outcomes in dystonia.

Deep Brain Stimulation↗

Deep brain stimulation of the subthalamic nucleus for control of extrapyramidal features in advanced idiopathic parkinson's disease: one year follow-up.

UNLABELLED: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) with a quadripolar electrode was carried out in 9 patients with advanced idiopathic Parkinson's disease (PD) affected with severe diurnal motor fluctuations. The effect of bilateral STN stimulation was evaluated by clinical methods in all patients after 3 and 12 months. Assessment was based on the Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests, the Schwab and England Activities of Daily Living and a diary chart to document motor fluctuations. Alterations in parkinsonian signs, motor performance and functional outcome were recorded postoperatively (1) under temporary complete withdrawal of both STN stimulation and medication; (2) in the presence of STN stimulation only; and (3) in the presence of both STN stimulation and medication. The results were compared with the preoperative data assessed in defined on-phase and defined off-phase. STN stimulation on (compared to STN stimulation off) results in a significant improvement in UPDRS motor scores: after 3 months from 50.5 +/- 14.3 to 27.8 +/- 5.8, and after 12 months from 49.4 +/- 14.1 to 27.1 +/- 7.1 (p < 0.01). There was a significant decrease in the average duration of off-periods from 8.82 +/- 2.47 hours to 1.00 +/- 1.06 hours (p < 0.001), a marked increase in on-periods without dyskinesia from 4.62 +/- 2.72 to 14.62 +/- 1.51 hours (p < 0.01), and a sharp drop in on-periods with dyskinesia from 2.87 (+/- 4.18) to 0.25 (+/- 0.97) hours (p < 0.05), which remained stable up to 12 months (off-periods: 1.25 +/- 1.58 hours, p < 0.001; on-periods without: 13.87 +/- 1.95 hours, p < 0.001; and on-periods wth dyskinesia: 0.37 +/- 1.06 hours, p < 0.05). However, our first PD patient with an implanted DBS electrode within the STN died from cardiac infarction two days after surgery. This sudden death was not linked either to surgery nor to stimulation - and happened by chance. Our findings confirm that STN stimulation is a suitable functional neurosurgical procedure for the modulation and control of PD signs associated with severe motor fluctuations, in that they demonstrate a beneficial effect which was fully sustained over a one year follow-up period. KEYWORDS: Subthalamic nucleus, deep brain stimulation, Parkinson's disease.

Activities of Daily Living↗

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: evaluation of active electrode contacts.

BACKGROUND: The subthalamic nucleus is the preferred target for deep brain stimulation in patients with advanced Parkinson's disease. The site of permanent stimulation is the subject of ongoing debate, as stimulation both within and adjacent to the subthalamic nucleus may be effective. OBJECTIVE: To assess the position of active electrode contacts in relation to the dorsal margin of the subthalamic nucleus as determined by intraoperative microrecordings and magnetic resonance imaging (MRI). METHODS: In 25 patients suffering from severe levodopa sensitive parkinsonism, deep brain stimulating electrodes (n = 49) were implanted following mapping of the subthalamic nucleus by microrecording and microstimulation along five parallel tracks. Postoperative stereotactic radiography and fusion of pre- and postoperative MRI studies were used to determine the stereotactic position relative to the midcommissural point of the most effective electrode contacts selected for permanent stimulation (n = 49). Intraoperative microrecordings were analysed retrospectively to define the dorsal margin of the subthalamic nucleus. In cases where the dorsal margin could be defined in at least three microrecording tracks (n = 37) it was correlated with the position of the active contact using an algorithm developed for direct three dimensional comparisons. RESULTS: Stimulation of the subthalamic nucleus resulted in marked improvement in levodopa sensitive parkinsonian symptoms and levodopa induced dyskinesias, with significant improvement in UPDRS III scores. In several instances, projection of the electrode artefacts onto the T2 weighted MRI visualised subthalamic nucleus of individual patients suggested that the electrodes had passed through the subthalamic nucleus. When the actual position of active electrode contacts (n = 35) was correlated with the dorsal margin of the subthalamic nucleus as defined neurophysiologically, most contacts were located either in proximity (+/- 1.0 mm) to the dorsal border of the subthalamic nucleus (32.4%) or further dorsal within the subthalamic region (37.8%). The other active contacts (29.7%) were detected within the dorsal (sensorimotor) subthalamic nucleus. The average position of all active contacts (n = 49) was 12.8 mm (+/- 1.0) lateral, 1.9 mm (+/- 1.4) posterior, and 1.6 mm (+/- 2.1) ventral to the midcommissural point. CONCLUSIONS: Subthalamic nucleus stimulation appears to be most effective in the border area between the upper subthalamic nucleus (sensorimotor part) and the subthalamic area containing the zona incerta, fields of Forel, and subthalamic nucleus projections.

Aged↗

Pallidal deep-brain stimulation in primary generalized or segmental dystonia.

BACKGROUND: Neurostimulation of the internal globus pallidus has been shown to be effective in reducing symptoms of primary dystonia. We compared this surgical treatment with sham stimulation in a randomized, controlled clinical trial. METHODS: Forty patients with primary segmental or generalized dystonia received an implanted device for deep-brain stimulation and were randomly assigned to receive either neurostimulation or sham stimulation for 3 months. The primary end point was the change from baseline to 3 months in the severity of symptoms, according to the movement subscore on the Burke-Fahn-Marsden Dystonia Rating Scale (range, 0 to 120, with higher scores indicating greater impairment). Two investigators who were unaware of treatment status assessed the severity of dystonia by reviewing videotaped sessions. Subsequently, all patients received open-label neurostimulation; blinded assessment was repeated after 6 months of active treatment. RESULTS: Three months after randomization, the change from baseline in the mean (+/-SD) movement score was significantly greater in the neurostimulation group (-15.8+/-14.1 points) than in the sham-stimulation group (-1.4+/-3.8 points, P<0.001). During the open-label extension period, this improvement was sustained among patients originally assigned to the neurostimulation group, and patients in the sham-stimulation group had a similar benefit when they switched to active treatment. The combined analysis of the entire cohort after 6 months of neurostimulation revealed substantial improvement in all movement symptoms (except speech and swallowing), the level of disability, and quality of life, as compared with baseline scores. A total of 22 adverse events occurred in 19 patients, including 4 infections at the stimulator site and 1 lead dislodgment. The most frequent adverse event was dysarthria. CONCLUSIONS: Bilateral pallidal neurostimulation for 3 months was more effective than sham stimulation in patients with primary generalized or segmental dystonia. (ClinicalTrials.gov number, NCT00142259 [ClinicalTrials.gov].).

Adult↗

Bilateral subthalamic nucleus deep brain stimulation in a patient with cervical dystonia and essential tremor.

The role of subthalamic nucleus (STN) deep brain stimulation (DBS) is well established in Parkinson's disease, but experience with STN DBS in other movement disorders is limited. We report on a patient with medically refractory cervical dystonia and essential tremor resulting in dystonic head tremor and action tremor of the hands who obtained complete tremor suppression and near resolution of her cervical dystonia with bilateral STN stimulation. The results in this case demonstrate that STN DBS can dramatically improve dystonia and tremor in nonparkinsonian movement disorders.

Adult↗

Targets for deep brain stimulation in Parkinson's disease.

The use of stimulation electrodes implanted in the brain to control severely disabling neurological and psychiatric conditions is an exciting and fast emerging area of neuroscience. An excellent example is Parkinson's disease (PD), in which tens of thousands of patients have now been implanted with stimulation electrodes. Patients with PD underwent deep brain stimulation (DBS) at the level of the thalamus, globus pallidus internus, subthalamic nucleus, pedunculopontine nucleus and prelemniscal radiation. The results of these interventions revealed that each target has its own specific stimulation-related positive and negative effects. Clinicians can choose their DBS target based on the situation of their individual PD patients. In the authors' opinion, patient-specific targeting should be preferred over disease-specific targeting. In this review, the authors give an overview of the targets that have been used for DBS in PD and discuss patient-specific targeting.

Deep Brain Stimulation↗

Bilateral effects of unilateral subthalamic nucleus deep brain stimulation in advanced Parkinson's disease.

To investigate the bilateral effects of unilateral subthalamic nucleus deep brain stimulation (STN-DBS), we prospectively studied 9 consecutive advanced Parkinson's disease (PD) patients (2 men and 7 women) who underwent unilateral STN-DBS. Patients were evaluated preoperatively and at 3 and 6 months postoperatively with and without dopaminergic medications ('on' and 'off' medication, respectively). Postoperatively, patients were assessed with and without stimulation. We found that, when compared with baseline, the 'off' medication scores of the Unified Parkinson's Disease Rating Scale motor part (UPDRS III) and activities of daily living (UPDRS II) were improved by 37% (p = 0.028) and 50% (p = 0.046) at 6 months after surgery, respectively. Stimulation while 'off' medication improved the total UPDRS score by 42% (p = 0.028) at 6 months. At 6 months after surgery, the subscore of UPDRS III of body parts contralateral to the DBS implantation had improved by 48% (p = 0.028), and the ipsilateral subscore of UPDRS III and the axial subscore of UPDRS III had improved by 20% (p = 0.027) and 39% (p = 0.028), respectively. Daily dosage of levodopa was reduced by 15% at 6 months. No patient exhibited permanent side effects. These findings indicate that unilateral STN-DBS may be a reasonable surgical procedure for selected PD patients who have markedly asymmetric parkinsonism.

Activities of Daily Living↗

Deep brain stimulation for neuropathic cephalalgia.

The aim of this study was to determine the efficacy of deep brain stimulation (DBS) in the treatment of various types of intractable head and facial pains. Seven patients underwent the insertion of DBS electrodes into the periventricular/periaqueductal grey region and/or the ventroposteromedial nucleus of the thalamus. We have shown statistically significant improvement in pain scores (visual analogue and McGill's) as well as health-related quality of life (SF-36v2) following surgery. There is wide variability in patient outcomes but, overall, DBS can be an effective treatment. Our results are compared with the published literature and electrode position for effective analgesia is discussed.

Adult↗

Subthalamic deep brain stimulation in patients with a previous pallidotomy.

The safety and efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) in patients who have had a previous unilateral pallidotomy is not clear. We identified 10 patients (9 male) at the Baylor College of Medicine Parkinson's Disease Center who underwent STN DBS after prior unilateral pallidotomy. Demographics, efficacy as determined by off Unified Parkinson's Disease Rating Scale (UPDRS) part III scores, and levodopa equivalent dosing were analyzed. We then compared these to an age- and sex-matched group of 25 DBS patients who had no prior pallidotomy. After their initial pallidotomy (mean age, 51.8 +/- 10.8 years), the mean UPDRS motor off medicine scores improved from 51.3 +/- 14.3 to 34.9 +/- 12.8, and the UPDRS dyskinesia score improved from 1.8 +/- 1.0 to 0.8 +/- 0.7. Their STN DBS off UPDRS motor scores (mean age, 56.0 +/- 10.2 years) improved by 16.0% from 53.1 +/- 9.7 (range, 42-68) to 44.6 +/- 11.1 (range, 25-67). In contrast, the UPDRS off motor scores in a control group of 25 DBS patients improved by 49.9%, from 49.7 +/- 11.1 to 25.7 +/- 18.9, (16.0% vs. 49.9%; P < 0.001). Changes in UPDRS dyskinesia scores were similar in both groups. AE thought to be related to the STN DBS following pallidotomy included worse dysarthria (three) and worse balance (two). STN DBS patients with prior pallidotomy had less improvement in UPDRS off motor score compared to other STN DBS patients, despite relatively good outcomes immediately after their pallidotomy. This may be partially due to a selection bias, but it may also indicate that prior pallidotomy is a negative predictor of outcome of STN DBS and should be considered in patient selection.

Adult↗

Effects of thalamic deep brain stimulation based on tremor type and diagnosis.

It has been suggested that deep brain stimulation (DBS) is less effective in alleviating proximal than distal postural arm tremor reduction is said to be less in essential tremor (ET) than in Parkinson's disease (PD). We analyzed blinded rater's tremor scores and subjects' disability ratings at 3-month follow-up to examine the effects of DBS based on tremor type (rest, kinetic, distal postural, proximal postural) and diagnosis (ET, PD). An independent examiner provided tremor scores using randomized videotaped footage of 19 ET and 10 PD subjects at baseline and at follow-up with DBS "on." Subjects provided self-ratings of disability at baseline and at follow-up. Comparisons of baseline and follow-up tremor scores and disability ratings were made using the Mann-Whitney U and Wilcoxon rank sum W test; correlation analyses were performed using Spearman rank order correlation test. There were significant and essentially equal improvements in tremor scores of test, kinetic, distal postural, and proximal postural tremor at follow-up. Only one subject had no improvement in tremor. Tremor improved significantly and to the same extent in ET and PD subjects in each position except "at rest," which was most improved in PD (p = 0.0003). ET and PD subjects did not differ in the extent of disability improvement. Improved disability correlated only with improved postural tremor scores; proximal postural and distal postural (r = 0.41, p = 0.03; r = 0.47, p = 0.01). DBS is effective in alleviating tremor and disability in both ET and PD. Resting, kinetic, distal postural, and proximal postural tremor can be reduced to an equal degree. However, DBS produces the greatest improvement in disability in association with improved postural tremor in both ET and PD.

Adolescent↗